Cardiac Path Robbins Part 1 Flashcards
cardiac valves- tri-layered architecture
- dense collagenous core (fibrosa) at the outflow surface and connected to the valvular supporting structures
- central core of loose CT (spongiosa)
- layer rich in elastin (ventricularis or atrialis) on inflow surface
valves- critical to fxn
valvular interstitial cells (most abundant cell type in heart valves)
-syn ECM and express matrix degrading enzymes
pathologic changes to valves- 3 types
- damage to collagen that weakens the leaflets (example- mitral valve prolapse)
- nodular calcification beginning in interstitial cells (calcific aortic stenosis)
- fibrotic thickening (rheumatic heart disease)
components of conduction system
- SA node
- AV node
- bundle of HIS (connects right atrium to ventricular septum)
- purkinje network
3 major epicardial coronary a’s
- LAD (left ant descending) and LCX (left circumflex) a’s arise from left coronary a
- right coronary a
LAD and LCX divisions
- LAD- diagonal branches
- LCX- marginal branches
aging and the heart- myocardium and chambers
- dec LV chamber size (sigmoid septum- bulging of vasal ventricular septum into left ventricular outflow tract)
- inc epicardial fat
- myocardial changes:
- lipofuscin and basophilic degeneration (gray-blue byproduct of glycogen metabolism)
- fewer myocytes, inc collagen fibers
aging and the heart- valves
- aortic and mitral valve annular calcification
- fibrous thickening
- mitral valve leaflets buckling towards left atrium- inc left atrium size
- lambl excrescences (small filiform processes on the closure lines of aortic and mitral valves- due to small thrombi)
aging and the heart- vascular changes
- coronary atherosclerosis
- stiffening of aorta
cardiovascular dysfxn- 6 principal mech’s
- pump failure
- flow obstruction
- regurgitant flow
- shunted flow
- disorders of cardiac conduction
- rupture of the heart or a major vessel
Congestive HF
-when heart is unable to pump blood at a rate to meet peripheral demand, or can only do so with inc filling pressure
CHF- result from?
- loss of myocardial contractile fxn (systolic dysfxn)
- loss of ability to fill the ventricles during diastole (diastolic dysfxn)
CHF- mech’s that maintain arterial P and organ perfusion
- Frank-Starling mech- inc filling volumes dilate the heart- inc actin-myosin cross-bridge formation- enhance contractility/SV
- myocardial adaptations- hypertrophy w/ or w/o cardiac chamber dilation
- act of neurohumoral systems- NE inc HR, act of renin-ang-aldosterone system, release of ANP
cardiac hypertrophy- caused by
- sustained inc in mechanical work due to P or volume overload
- trophic signals (B-R’s)
cardiac myocytes become hypertrophic when?
- sustained pressure or volume overload
- sustained trophic signals (B-adrenergic stim)
pressure overload- causes what?
- myocytes become thicker
- left ventricular wall thickness inc concentrically
volume overload- causes what?
- myocytes elongate
- ventricular dilation
cardiac hypertrophy- accompanied by?
- not accompanied by a inc in blood supply
- vulnerable to ischemia-related decompensation
best measure of hypertrophy
heart weight (rather than wall thickness)
the molecular/cellular changes in hypertrophied hearts that initially mediate enhanced fxn may contribute to the development of HF- thru?
- abnormal myocardial metabolism
- alterations of intracellular handling of ca ions
- myocyte apoptosis
- reprogramming of gene expression
increases cardiac work, causing hypertrophy
- HTN (p overload)
- valvular disease (p and or volume overload)
- MI (volume overload)
CHF- characterized by?
- dec CO and tissue perfusion (forward failure)
- pooling of blood in venous capacitance system (backward failure)- causes pulm edema and/or peripheral edema
left-sided heart failure- most commonly a result of?
(can be systolic or diastolic failure)
- MI
- HTN
- left-sided valve disease
- primary myocardial disease
left-sided heart failure- clinical effects are due to?
- congestion in pulm circulation
- stasis of blood in left-sided chambers
- dec tissue perfusion
left-sided heart failure- morphologic changes
- left ventricular hypertrophy
- left ventricular dysfxn- left atrial dilation (leads to atrial fibrillation, stasis, thrombus)
- pulm congestion and edema (cough, dyspnea, orthopnea, paroxysmal nocturnal dyspnea)
- heart failure cells (hemosiderin-laden macrophages)- signs of pulm edema!!
left-sided heart failure- dec ejection fraction may result in?
- dec glomerular perfusion- stim release of renin- inc volume- prerenal azotemia
- dec cerebral perfusion-hypoxic encephalopathy
left-sided HF- divided into
- systolic failure- insuff ejection fraction
- diastolic failure- abnormally stiff and cannot relax during diastole- heart unable to inc its output in response to inc metabolic demands of peripheral tissues- cant expand normally so any inc in filling P goes back to pulm circulation (flash pulm edema)
diastolic failure- most common in?
- > 65 age, women
- HTN- most common cause!!
- diabetes, obesity, b/l renal a stenosis
right-sided heart failure (cor pulmonale)- most common cause is?
-left-sided failure!!
isolated right-sided HF- results from?
any cause of pulm HTN!!!!
- parenchymal lung diseases
- primary pulm HTN
- pulm vasoconstriction
primary right-sided HF
- pulm congestion is minimal
- venous system is markedly congested: liver congestion, splenic congestion, effusions in peritoneal, pleural, pericardial spaces, edema, renal congestion
right-sided HF- morphology
- congestive hepatomegaly- red/brown pericentral zones- “nutmeg liver”
- centrilobular necrosis- when left-sided HF w/ hypoperfusion is present
- cardiac cirrhosis- longstanding HF
- congestive splenomegaly
- effusions in peritoneal, pleural and pericardial spaces
- edema of peripheral and dependent portions of body (ankles)- hallmark!!
- generalized edema may occur (anasarca)
ischemic heart disease- may result in?
- MI
- angina pectoris
- chronic ischemic heart disease, with HF
- sudden cardiac death
leading cause of death in US?
ischemic heart disease (90% secondary to atherosclerosis)
- chronic vascular occlusion
- acute plaque change- thrombus
most common type of pediatric heart disease
-congenital CV malformations
1st and 2nd heart fields- express?
- 1st heart field- Hand1 TF
- 2nd heart field- Hand2 and GF-10
1st and 2nd heart field- becomes?
- 1st heart field- left ventricle
- 2nd heart field- outflow tract, right ventricle, atria
2 critical events that occur by day 28
(when initial cell crescent develops into a beat in tube- loops to right and begins to form the basic heart chambers 8 days later)
- neural crest-derived cells migrate into the outflow tract- participate in the septation of the outflow tract and the formation of the aortic arches
- interstitial CT that will become the AV canal and outflow tract enlarges to produce endocardial cushings
proper development of heart- depends on what TFs?
-Wnt, hedgehog, VEGF, bone morphogenetic factor, TGFB, fibroblast GF, Notch pathways
development of heart- day 15
-first heart field (FHF) cells form a crescent shape in the ant embryo with second heart field (SHF) cells
development of heart- day 21
-SHF cells lie dorsal to the straight heart tube, begin to migrate into the ant and posterior ends of the tube to from the right ventricle, conotruncus , and part of atria
development of heart- day 28
-cardiac neural crest cells migrate into the outflow tract from the neural folds to septate the outflow tract and pattern the bilaterally symmetric aortic arch a’s
development of heart- day 50
-septation of ventricles, atria, and AV valves results in the 4-chambered heart
major known cause of congenital heart disease
sporadic genetic abnormalities
3 TFs that are mutated in some pts with atrial and ventricular septal defects
- GATA4, TBX5, NKX2-5
- bind together and co-reg the expression of target genes
deletion of chromosome 22q11.2- what syndrome?
(50% of pts with DiGeorge syndrome)
- 4th branchial arch and derivatives of the 3rd and 4th pharyngeal pouches (formation of thymus, parathyroids, heart) develop abnormally
- CATCH-22- cardiac abnormality, abnormal facies, thymic aplasia, cleft palate, hypocalcemia; all on chrom 22!
- due to deletion of TBX1 (reg neural crest migration)
most common genetic cause of congenital heart disease is?
- trisomy 21 (down syndrome)- 40% of pts have heart defect
- most often involves structures form second hart field
congenital heart disease- structural abnormalities divided into 3 categories
- left-to-right shunt
- right-to-left shunt
- obstruction
shunt- is what?
abnormal communication b.w chambers or BVs
right-to-left shunt
- hypoxia and cyanosis results (pulm circulation is bypassed)
- allow emboli from peripheral v’s to bypass the lungs and go into systemic circulation (paradoxical embolism)
- long standing cyanosis causes -hypertrophic osteoarthropathy (clubbing of fingers/toes) and polycythemia
most important causes of right-to-left shunt
- Tetralogy of Fallot
- transposition of great a’s
- persistent truncus arteriosus
- tricuspid atresia
- total anomalous pulm venous connection
left-to-right shunts
- inc pulmonary blood flow (but are not initially assoc with cyanosis)
- elevate volume and P in the normally low-P pulm circulation
- muscular pulm a’s respond by medial hypertrophy and vasoconstriction- causes obstructive intimal lesions
- right ventricle hypertrophy
- eventually, pulm vascular resistance approaches systemic levels, so becomes a right-to-left shunt (Eisenmenger syndrome)
obstructive congenital heart disease
-complete obstrudction- atresia
left-to-right shunts; includes?
- most common congenital heart disease
- ASD (atrial septal defect)
- VSD (ventricular septal defect)
- PDA (patent ductus arteriosus)
atrial septal defect
- caused by incomplete tissue formation- allows communication of blood b/w left and right atria
- usually asymptomatic until adulthood
- shouldnt be confused with PFO (patent foramen ovale)
ASD and PFO- defects in the formation of interatrial septum- developmental stages of this structure:
- septum primum- partially separates the atria (anterior opening- ostium primum)
- septum primum develops a second posterior opening- ostium secundum (septum secundum- ingrowth to right and anterior of septum primum)
- foramen ovale is continuous with the ostium secundum
- septum secundum enlarges until it forms a flap of tissue that covers the foramen ovale- which closes in response to P gradients b/w atria
septum secundum and foramen ovale- what happens in fetal life and at birth?
- valve opens only when the P is greater in the right atrium
- in fetal life- lungs nonfxnal so the P in pulm circulation is greater than systemic circulation P- so the valve of the foramen ovale is open!!
- at birth- lungs expand- pulm vascular P’s drop- so rt atrial Ps drop below the left atrium P- foramen ovale closes!
ASDs- morphology
- secundum ASD (90%)- deficient formation near the center of the atrial septum; not assoc with other anomalies
- primum anomalies (5%)- occur adj to AV valves, often assoc with AV valve abnormalities and a VSD
- sinus venous defects (5%)- near the entrance of SVC- assoc with anomalous pulm venous return to rt atrium
ASDS- clinical features
- left-to-right shunt (b/c systemic vascular R > pulm vascular R and right ventricle compliance is greater than the left)
- pulm blood flow 2-8x more than normal
- murmur due to flow thru the pulm valve and ASD
- well tolerated!
- not symptomatic until age 30
- low mortality
patent foramen ovale
- closes in 80% of ppl by 2 yrs of age
- unsealed flap can open if right-sided P’s become elevated
- sustained pulm HTN or transient (sneeze, cough)- could cause a paradoxical embolism due to right-to-left shunting
Ventricular septal defect- morphology
- most common form of congenital heart disease
- 90%- membranous VSD- occur in the region of membranous interventricular septum
- remainder- infundibular VSD- below the pulm valve or within the muscular septum
VSD- clinical features
- most that manifest in kids are assoc with other cardiac anomalies (Tertralogy of Fallot)
- if first detected in an adult- usually an isolated defect!
- 50% of small VSDs close spontaneously
- large defects cause left-to-right shunting- right ventricular hypertrophy and pulm HTN!- can reverse flow thru shunt- cyanosis!!
patent ductus arteriosus
- arises from pulm aorta and joins the aorta
- in fetus life- permits blood flow from pulm a to aorta (bypasses the unoxygenated lungs)
- after birth- closes in 1-2 days (due to dec pulm vascular R, dec PGE2)
- closes- forms ligamentum arteriosum
- ductal closure delayed in infants with hypoxia or when PDA occurs in assoc with other defects (VSDs that inc Pulm vascular P’s)
patent ductus arteriosus- clinical
- harsh “machinery-like” murmur
- usually asymptomatic at birth
- no cyanosis b/c the shunt is initially left-to-right
- should close it as early in life as possible!!
- keeping it open may save infants with other malformations
